Idiopathic growth hormone (GH) deficiency is a clinically and biologically heterogeneous condition. This study evaluates the capacity of the initial growth response to hGH therapy to distinguish certain from transient GH deficiency. Twenty-five patients having a GH peak < 10 μg/l after 2 pharmacological stimulation tests were classified according to the accuracy of the diagnosis of GH deficiency. Group 1 (n = 17) had certain GH deficiency because of pituitary stalk interruption syndrome and/or familial form. Group 2 (n = 8) had a transient GH deficiency. The mean increase in height standard deviation (SD) was 1.3 ± 0.1 (mean ± SE) and 0.5 ± 0.1 during the first and second years in group 1 and 0.4 ± 0.1 (p < 0.0005, compared to group 1) and 0.1 ± 0.2 (p < 0.025 compared to group 1) during the first and second years in group 2. During the first year of therapy, the increase in height was > 1 SD in 14 patients of group 1 and in 1 patient of group 2. In group 1, this increase was positively correlated with an increase in body mass index (r = 0.80, p < 0.01) during the first year and with target height (r = 0.60, p < 0.02) during the second year. Growth rate (SD for age) during the first year in this group was negatively correlated with the height prior to therapy (r = -0.72, p < 0.005). In group 2, the increase in height was positively correlated with the growth rate before therapy (r = 0.74, p < 0.05) during the first year and with the hGH dose (r = 0.90, p < 0.025) during the second year. We conclude that the growth response during the first year of hGH therapy, interpreted according to the height before therapy, is a good criterion of GH deficiency and that the change in weight influences the growth response in certain GH deficiency. The group of transient GH deficiency emphasizes the need to perform additional evaluations of GH secretion in children having GH deficiency without anatomical lesion and increase in height lower than 1 SD during the first year of hGH therapy.